{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:16:29Z","timestamp":1789215389115,"version":"build-2803163510"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T00:00:00Z","timestamp":1366675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0062187","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T17:50:15Z","timestamp":1366739415000},"page":"e62187","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":105,"title":["Lipopolysaccharide Disrupts the Milk-Blood Barrier by Modulating Claudins in Mammary Alveolar Tight Junctions"],"prefix":"10.1371","volume":"8","author":[{"given":"Ken","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Oyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Numata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Morshedur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruto","family":"Kumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,4,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10911-011-9231-3","article-title":"Mastitis and its impact on structure and function in the ruminant mammary gland","volume":"16","author":"RM Akers","year":"2011","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref2","first-page":"727","article-title":"Management of mastitis in breastfeeding women","volume":"78","author":"JP Spencer","year":"2008","journal-title":"Am Fam Physician"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s10911-011-9235-z","article-title":"Mastitis therapy and antimicrobial susceptibility: a multispecies review with a focus on antibiotic treatment of mastitis in dairy cattle","volume":"16","author":"J Barlow","year":"2011","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"826","DOI":"10.3168\/jds.S0022-0302(88)79623-X","article-title":"Relationship of milk proteins in blood with somatic cell counts in milk of dairy cows","volume":"71","author":"TB McFadden","year":"1988","journal-title":"J Dairy Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3168\/jds.S0022-0302(87)80005-X","article-title":"Alpha-lactalbumin in bovine serum: relationships with udder development and function","volume":"70","author":"TB McFadden","year":"1987","journal-title":"J Dairy Sci"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Burton JL, Erskine RJ (2003) Immunity and mastitis. Some new ideas for an old disease. Vet Clin North Am Food Anim Pract 19: 1\u201345, v.","DOI":"10.1016\/S0749-0720(02)00073-7"},{"key":"ref7","first-page":"13P","article-title":"Changes in mammary gland permeability at the onset of lactation in the goat: an effect on tight junctions?","volume":"230","author":"JL Linzell","year":"1973","journal-title":"J Physiol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3168\/jds.S0022-0302(98)75594-8","article-title":"No evidence for basolateral secretion of milk protein in the mammary gland of lactating goats","volume":"81","author":"K Stelwagen","year":"1998","journal-title":"J Dairy Sci"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1677\/joe.0.1590173","article-title":"Elevated plasma cortisol reduces permeability of mammary tight junctions in the lactating bovine mammary epithelium","volume":"159","author":"K Stelwagen","year":"1998","journal-title":"J Endocrinol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1749-6632.2000.tb05235.x","article-title":"The structure and function of claudins, cell adhesion molecules at tight junctions","volume":"915","author":"S Tsukita","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1097\/00075197-200211000-00012","article-title":"Intestinal barrier function","volume":"5","author":"DC Baumgart","year":"2002","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"7844","DOI":"10.1128\/IAI.73.12.7844-7852.2005","article-title":"Helicobacter pylori activates myosin light-chain kinase to disrupt claudin-4 and claudin-5 and increase epithelial permeability","volume":"73","author":"JP Fedwick","year":"2005","journal-title":"Infect Immun"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3945\/jn.110.135657","article-title":"Regulation of tight junction permeability by intestinal bacteria and dietary components","volume":"141","author":"D Ulluwishewa","year":"2011","journal-title":"J Nutr"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1083\/jcb.201106011","article-title":"Impenetrable barriers or entry portals? The role of cell-cell adhesion during infection","volume":"195","author":"M Bonazzi","year":"2011","journal-title":"J Cell Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bbamem.2007.08.017","article-title":"Transmembrane proteins of tight junctions","volume":"1778","author":"H Chiba","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/MNH.0b013e32820ac97d","article-title":"Claudins and paracellular transport: an update","volume":"16","author":"S Angelow","year":"2007","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.tcb.2006.02.006","article-title":"Claudins in occluding junctions of humans and flies","volume":"16","author":"M Furuse","year":"2006","journal-title":"Trends Cell Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1083\/jcb.153.2.263","article-title":"Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells","volume":"153","author":"M Furuse","year":"2001","journal-title":"J Cell Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10911-009-9131-y","article-title":"Cell contacts in the mouse mammary gland: i. Normal gland in postnatal development and the secretory cycle. 1973","volume":"14","author":"DR Pitelka","year":"2009","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3168\/jds.S0022-0302(94)76969-1","article-title":"Mammary epithelial cell tight junction integrity and mammary blood flow during an extended milking interval in goats","volume":"77","author":"K Stelwagen","year":"1994","journal-title":"J Dairy Sci"},{"key":"ref21","first-page":"R379","article-title":"Time course of milk accumulation-induced opening of mammary tight junctions, and blood clearance of milk components","volume":"273","author":"K Stelwagen","year":"1997","journal-title":"Am J Physiol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00418-011-0863-6","article-title":"Distinct behavior of claudin-3 and -4 around lactation period in mammary alveolus in mice","volume":"136","author":"K Kobayashi","year":"2011","journal-title":"Histochem Cell Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s00535-011-0390-1","article-title":"Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease","volume":"46","author":"M Oguro","year":"2011","journal-title":"J Gastroenterol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1007\/s00401-003-0688-z","article-title":"Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme","volume":"105","author":"H Wolburg","year":"2003","journal-title":"Acta Neuropathol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s10911-011-9236-y","article-title":"Molecular epidemiology of mastitis pathogens of dairy cattle and comparative relevance to humans","volume":"16","author":"RN Zadoks","year":"2011","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.domaniend.2003.09.003","article-title":"Short-term changes of mRNA expression of various inflammatory factors and milk proteins in mammary tissue during LPS-induced mastitis","volume":"26","author":"S Schmitz","year":"2004","journal-title":"Domest Anim Endocrinol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1017\/S0022029909004129","article-title":"Cell population, viability, and some key immunomodulatory molecules in different milk somatic cell samples in dairy cows","volume":"76","author":"A Baumert","year":"2009","journal-title":"J Dairy Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"5405","DOI":"10.3168\/jds.2010-3931","article-title":"Lipopolysaccharide and lipoteichoic acid induce different immune responses in the bovine mammary gland","volume":"94","author":"O Wellnitz","year":"2011","journal-title":"J Dairy Sci"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00424-011-1034-2","article-title":"Altered expression of tight junction proteins in mammary epithelium after discontinued suckling in mice","volume":"463","author":"AG Markov","year":"2012","journal-title":"Pflugers Arch"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1089\/dna.2006.25.79","article-title":"Differential expression of claudin 1, 3, and 4 during normal mammary gland development in the mouse","volume":"25","author":"AA Blanchard","year":"2006","journal-title":"DNA Cell Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1677\/joe.0.1700347","article-title":"Hormonal regulation of tight junction closure in the mouse mammary epithelium during the transition from pregnancy to lactation","volume":"170","author":"DA Nguyen","year":"2001","journal-title":"J Endocrinol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"C1213","DOI":"10.1152\/ajpcell.00558.2003","article-title":"The tight junction: a multifunctional complex","volume":"286","author":"EE Schneeberger","year":"2004","journal-title":"Am J Physiol Cell Physiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cis.2012.01.002","article-title":"Casein micelles and their internal structure","volume":"171\u2013172","author":"CG de Kruif","year":"2012","journal-title":"Adv Colloid Interface Sci"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"35571","DOI":"10.1074\/jbc.M106013200","article-title":"Interleukin-2 receptor beta subunit-dependent and -independent regulation of intestinal epithelial tight junctions","volume":"276","author":"R Nishiyama","year":"2001","journal-title":"J Biol Chem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.bcp.2006.07.010","article-title":"Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity","volume":"72","author":"SL Doyle","year":"2006","journal-title":"Biochem Pharmacol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1023\/A:1018707309361","article-title":"Tight junction regulation in the mammary gland","volume":"3","author":"DA Nguyen","year":"1998","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref37","first-page":"1681","article-title":"Concomitant lipopolysaccharide-induced transfer of blood-derived components including immunoglobulins into milk. J Dairy Sci","volume":"96","author":"M Lehmann","year":"2012"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1007\/s11033-011-0870-7","article-title":"Role of post translational modifications and novel crosstalk between phosphorylation and O-beta-GlcNAc modifications in human claudin-1, -3 and -4","volume":"39","author":"AM Butt","year":"2012","journal-title":"Mol Biol Rep"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.yexcr.2003.12.014","article-title":"Thr203 of claudin-1, a putative phosphorylation site for MAP kinase, is required to promote the barrier function of tight junctions","volume":"295","author":"M Fujibe","year":"2004","journal-title":"Exp Cell Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"26233","DOI":"10.1074\/jbc.M502003200","article-title":"Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells","volume":"280","author":"T D'Souza","year":"2005","journal-title":"J Biol Chem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s10911-009-9130-z","article-title":"Changes in colostrum composition and in the permeability of the mammary epithelium at about the time of parturition in the goat. 1974","volume":"14","author":"JL Linzell","year":"2009","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"7412","DOI":"10.1074\/jbc.M110560200","article-title":"Molecular regulation of urothelial renewal and host defenses during infection with uropathogenic Escherichia coli","volume":"277","author":"IU Mysorekar","year":"2002","journal-title":"J Biol Chem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1007\/s13277-012-0493-1","article-title":"Anti-apoptotic effect of claudin-1 on TNF-alpha-induced apoptosis in human breast cancer MCF-7 cells","volume":"33","author":"Y Liu","year":"2012","journal-title":"Tumour Biol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"956897","DOI":"10.1155\/2010\/956897","article-title":"Claudin 1 in breast tumorigenesis: revelation of a possible novel &quot;claudin high&quot; subset of breast cancers","volume":"2010","author":"Y Myal","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1051\/vetres:2007047","article-title":"Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells","volume":"39","author":"EM Ibeagha-Awemu","year":"2008","journal-title":"Vet Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1111\/j.1462-5822.2008.01123.x","article-title":"In vivo imaging of NF-kappaB activity during Escherichia coli-induced mammary gland infection","volume":"10","author":"S Notebaert","year":"2008","journal-title":"Cell Microbiol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.intimp.2010.04.022","article-title":"Retinoic acid attenuates lipopolysaccharide-induced inflammatory responses by suppressing TLR4\/NF-kappaB expression in rat mammary tissue","volume":"10","author":"B Gu","year":"2010","journal-title":"Int Immunopharmacol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/jcp.21922","article-title":"Activation of nuclear factor kappa B in mammary epithelium promotes milk loss during mammary development and infection","volume":"222","author":"L Connelly","year":"2010","journal-title":"J Cell Physiol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00418-009-0674-1","article-title":"Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-kappaB in dendritic cells","volume":"133","author":"R Kamekura","year":"2010","journal-title":"Histochem Cell Biol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"158","DOI":"10.2353\/ajpath.2010.090548","article-title":"Epithelial NF-kappaB enhances transmucosal fluid movement by altering tight junction protein composition after T cell activation","volume":"176","author":"Y Tang","year":"2010","journal-title":"Am J Pathol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.2337\/db09-1606","article-title":"TNF-alpha signals through PKCzeta\/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability","volume":"59","author":"CA Aveleira","year":"2010","journal-title":"Diabetes"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.toxlet.2012.04.012","article-title":"Pro-inflammatory NF-kappaB and early growth response gene 1 regulate epithelial barrier disruption by food additive carrageenan in human intestinal epithelial cells","volume":"211","author":"HJ Choi","year":"2012","journal-title":"Toxicol Lett"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1023\/A:1018725207969","article-title":"NF-kappaB and apoptosis in mammary epithelial cells","volume":"4","author":"RW Clarkson","year":"1999","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1023\/B:JOMG.0000017431.45314.07","article-title":"The organization of tight junctions in epithelia: implications for mammary gland biology and breast tumorigenesis","volume":"8","author":"M Itoh","year":"2003","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.cimid.2007.10.004","article-title":"Inflammatory mediators in Escherichia coli-induced mastitis in mice","volume":"31","author":"S Notebaert","year":"2008","journal-title":"Comp Immunol Microbiol Infect Dis"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.cyto.2005.02.010","article-title":"Lipopolysaccharide and lipoteichoic acid induce different innate immune responses in bovine mammary epithelial cells","volume":"31","author":"Y Strandberg","year":"2005","journal-title":"Cytokine"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1749-6632.2009.04062.x","article-title":"Epithelial tight junctions in intestinal inflammation","volume":"1165","author":"JD Schulzke","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"ref58","first-page":"4093","article-title":"Corneal epithelial tight junctions and their response to lipopolysaccharide challenge","volume":"41","author":"X Yi","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.2353\/ajpath.2009.080973","article-title":"Alteration of tight junction proteins is an early event in psoriasis: putative involvement of proinflammatory cytokines","volume":"175","author":"N Kirschner","year":"2009","journal-title":"Am J Pathol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2174\/157015908785777210","article-title":"Brain endothelial cell-cell junctions: how to &quot;open&quot; the blood brain barrier","volume":"6","author":"SM Stamatovic","year":"2008","journal-title":"Curr Neuropharmacol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"5278","DOI":"10.4049\/jimmunol.167.9.5278","article-title":"Differential induction of endotoxin tolerance by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli","volume":"167","author":"M Martin","year":"2001","journal-title":"J Immunol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1111\/j.1462-5822.2007.00999.x","article-title":"Toll-like receptor 4 is needed to restrict the invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine model of acute mastitis","volume":"9","author":"E Gonen","year":"2007","journal-title":"Cell Microbiol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0165-0378(00)00064-4","article-title":"Cytokine production in chorioamnionitis","volume":"47","author":"F Saji","year":"2000","journal-title":"J Reprod Immunol"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jri.2008.04.002","article-title":"Inflammatory processes in preterm and term parturition","volume":"79","author":"I Christiaens","year":"2008","journal-title":"J Reprod Immunol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1051\/vetres:2003023","article-title":"Severity of E. coli mastitis is mainly determined by cow factors","volume":"34","author":"C Burvenich","year":"2003","journal-title":"Vet Res"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0062187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T16:05:52Z","timestamp":1595693152000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0062187"}},"subtitle":[],"editor":[{"given":"Bernhard","family":"Kaltenboeck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,4,23]]},"references-count":65,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2013,4,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0062187","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,23]]}}}